In an ion-trap time-of-flight mass spectrometer, ion-trap mass spectrometer or similar system, an ion trap is used to capture and confine ions by an effect of a radio-frequency electric field, to select an ion having a specific mass to-charge ratio m/z, and/or to break the thus selected ion into fragments. A typical example of the ion trap has a three-dimensional quadrupole configuration which consists of one ring electrode having an inner surface shaped like a hyperboloid of revolution of one sheet and a pair of end-cap electrodes having an inner surface shaped like a hyperboloid of revolution of two sheets facing each other across the ring electrode. Another commonly known example is a linear configuration consisting of four rod electrodes arranged parallel to each other. For convenience, the present description will hereinafter take the three-dimensional quadrupole ion trap as an example without specifically noting so. However, as will be explained later, the present invention can also be applied in a linear ion trap.
In the conventionally and commonly used type of ion trap, or the so-called analogue drive ion trap (which is hereinafter abbreviated as “AIT (analogue ion trap)” to clearly distinguish it from a DIT which will be mentioned later), a sinusoidal radio-frequency voltage is applied to the ring electrode to create an ion-capturing radio-frequency electric field within the space surrounded by the ring electrode and the end-cap electrodes and confine ions while oscillating them within that space by the effect of the radio-frequency electric field. Meanwhile, an ion trap which confines ions by applying a rectangular radio-frequency voltage to the ring electrode in place of the sinusoidal radio-frequency electric field has been developed in recent years (for example, see Patent Literature 1 or Non Patent Literature 1). This type of ion trap is normally called a digital ion trap (which is hereinafter abbreviated as DIT) since it uses a rectangular voltage having the binary voltage levels of “high” and “low.”
When an MS/MS analysis is performed in a mass spectrometer using a DIT (which is hereinafter abbreviated as the “DIT-MS”), after ions having a predetermined range of mass-to-charge ratios are captured within the inner space of the ion trap, a precursor-isolating (selecting) operation for discharging unnecessary ions from the ion trap must be performed so as to leave only an ion having a specific mass-to-charge ratio. For example, in the DIT-MS disclosed in Non Patent Literature 1, a precursor isolation using a high-speed technique called the rough isolation is initially performed, after which another precursor isolation with a higher level of resolving power is performed using a resonant excitation discharge by dipole excitation.
The rough isolation is a technique in which the precursor isolation is achieved by varying the applied voltage so as to shift the position of a line traversing a stability region on a stability diagram, which is prepared based on the stability condition for the solution of a Mathieu equation, and thereby change the lower limit mass (LMCO=low mass cut off) and the upper limit mass (HMCO=high mass cut off) of the ions that can be captured. Patent Literature 2 discloses an application of such a technique in an AIT. In a technique called DAWI (digital asymmetric waveform isolation) in Non Patent Literature 1 mentioned earlier as well as in Non Patent Literature 2, the duty ratio of the rectangular voltage is varied to change the LMCO and HMCO and thereby achieve by the precursor isolation.
One advantage of the DIT over the AIT is the high mass-separating power achieved by resonant excitation discharge. Normally, when the resonant excitation discharge is performed in a DIT, a rectangular-wave signal having a single frequency synchronized with the frequency of the rectangular voltage applied to the ring electrode is applied to the pair of end-cap electrodes (the single frequency is typically obtained by dividing the frequency of the aforementioned rectangular voltage). In this state, when the angular frequency of the rectangular voltage applied to the ring electrode is continuously decreased, the ions captured in the ion trap are sequentially and selectively subjected to resonant excitation in ascending order of their mass-to-charge ratios and discharged from the ion trap (forward scan). Conversely, when the frequency of the rectangular voltage applied to the ring electrode is continuously increased, the ions captured within the ion trap are sequentially and selectively subjected to resonant excitation in descending order of their mass-to-charge ratios and discharged from the ion trap (reverse scan). Accordingly, it is possible to achieve a high level of precursor-isolation power by successively performing the forward scan and the reverse scan by dipole excitation so as to leave only an ion having a desired mass-to-charge ratio within the ion trap.
However, there is the problem that a considerable amount of time is required if a method like the one described in Non Patent Literature 1 is used for the precursor isolation of a specific ion with high mass-separating power. This is due to the fact that, to assuredly remove unnecessary ions by the forward and backward scans, it is necessary to maintain the frequency for a predetermined discharge time for each unnecessary ion, and therefore, the rate of continuously changing the frequency must be decreased to a certain level or lower.
In a typical case, to achieve a sufficient mass-separating power, a period of time equal to or longer than several hundreds of milliseconds is required for only the precursor isolation. For example, in the DIT-MS in which the mass separation is performed in the ion trap itself, the MS/MS analysis is normally performed by the steps of: (A) capturing ions within a predetermined range of mass-to-charge ratios in the ion trap and cooling them; (B) performing an ion selection (the previously described precursor isolation) so as to leave only a desired precursor ion within the ion trap; (C) fragmenting the precursor ion by collision induced dissociation; and (D) causing a resonant discharge of the product ions produced by the fragmentation and obtaining a mass spectrum. Among these processes, each of the processes (A), (C) and (D) only requires a few to several tens of milliseconds. Accordingly, consuming several hundreds of milliseconds for only process (B) will significantly lower the throughput of the analysis. In recent years, improving the throughput of an analysis has been extremely important in the field of mass spectrometry, and time reduction of the precursor isolation in the DIT is a critical and unavoidable problem.
Methods for performing precursor isolation in an ion trap are not limited to the previously described ones; some other techniques are also commonly known. For example, for AITs, a precursor isolation technique has been commonly known which uses the relationship that the oscillation frequency of ions changes depending on the amplitude of the radio-frequency voltage applied to the ring electrode. In this technique, various kinds of unnecessary ions other than the target ion (precursor ion) are simultaneously removed by applying to the end-cap electrodes a signal having a broad-band frequency spectrum with a notch (omission) at the oscillation frequency of the target ion. One example of the signals commonly used as the aforementioned broad-band signal is an FNF (filtered noise field) signal described in Patent Literature 3. Another known example is a SWIFT (stored wave inverse Fourier transform) signal described in Patent Literature 4.
The techniques described in those literatures are intended for use in the AIT. However, the DIT also allows the use of an FNF signal or similar broad-band signal to achieve precursor isolation as in the case of the AIT. For example, Patent Literature 3 discloses a specific technique and system configuration for applying the precursor isolation using an FNF signal in the DIT. Although such a precursor isolation technique can be used as the aforementioned rough isolation, it is difficult to use this technique as the high-resolution precursor isolation which follows the rough isolation, since its resolving power is insufficient.